Curr Rheumatol Rep (2013) 15:346 DOI 10.1007/s11926-013-0346-y

SERONEGATIVE ARTHRITIS (MA KHAN, SECTION EDITOR)

Spondyloarthritis Associated with Conglobata, Suppurativa and Dissecting of the Scalp: A Review with Illustrative Cases

Debbie T. Lim & Neena M. James & Sobia Hassan & Muhammad A. Khan

# Springer Science+Business Media New York 2013

Abstract To review and highlight the association of acne and inadequately managed include: acne conglobata, conglobata, , and dissecting cellulitis of hidradenitis suppurativa, and dissecting cellulitis of the scalp the scalp with inflammatory arthritic conditions, we report five [1–15, 16•, 17••, 18]. In this review, we first briefly describe illustrative patients with this association, and a review of the the dermatologic manifestations of these diseases, and provide literature. All our patients were African-American males, and five illustrative case reports of the patients encountered at our their skin disease present before the onset of arthritis. Both center to highlight the clinical spectrum of the associated asymmetric peripheral arthritis and axial disease can occur. The inflammatory arthritis. This is followed by the description of arthritis is usually insidious and lacks association with the clinical, laboratory and radiographic findings of the rheumatoid factor and HLA-B27. Imaging of peripheral joints associated inflammatory arthritis and its management. can reveal erosions, periosteal bone reaction and new bone formation. When the axial skeleton is involved, imaging can reveal sacroiliitis, syndesmophyte formation. NSAIDs, oral and Acne Conglobata intra-articular steroids, DMARDs and TNF alpha antagonists have all been used with success. Controlled trials with larger Acne conglobata is a highly inflammatory form of acne numbers of patients are needed to assess which treatment which usually presents as numerous comedones, nodules, options are the most effective for this group of patients. papules, pustules, interconnecting and draining sinus tracts with associated scarring of the skin. Deep ulcers Keywords Ankylosing spondylitis . Sacroiliitis . may form beneath the nodules leading to keloid-type scars. Spondyloarthropathy . Seronegative arthritis . Treatment . Occasionally, acne conglobata may develop in the setting of TNF-inhibitors . HLA-B27 . Acne conglobata . Hidradenitis acne vulgaris that had been dormant for many years [19]. suppurativa . Dissecting cellulitis of the scalp . Inflammatory The lesions are usually found on the face, neck, chest, upper arthritic arms, buttocks and thighs. It is most common in teenage males but can occur in either sex and into adulthood [20]. This condition is different from , the most Introduction severe form of nodular acne, which is often classified with acne conglobata in the medical literature. Initially, the Dermatological diseases that show an association with disease resembles acne conglobata with numerous lesions seronegative inflammatory arthritis but are under-recognized on the back and chest, although the neck and face are invariably spared. The distinguishing morphologic feature This article is part of the Topical Collection on Seronegative Arthritis is the formation of hemorrhagic nodules and plaques which D. T. Lim : N. M. James : S. Hassan : M. A. Khan (*) later ulcerate [21]. The onset of acne fulminans is more Division of Rheumatology, Case Western Reserve University explosive, nodules and comedones are less common, School of Medicine, MetroHealth Medical Center, ulcerative and crusted lesions are unique, and systemic 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA symptoms such as fever, leukocytosis, polyarthralgia, e-mail: [email protected] myalgia, hepatosplenomegaly, and anemia are more 346, Page 2 of 8 Curr Rheumatol Rep (2013) 15:346 common [20]. It almost exclusively occurs in young men Caucasian male with acne conglobata and associated aged 13–16 years [21]. arthritis in both ankles [3]. In 1981, one of us (M.A.K.) reported at the Cleveland Society of Rheumatology meeting of an African-American Hidradenitis Suppurativa patient with HLA-B27 negative Reiter’s-like reactive arthritis in association with hidradenitis suppurativa and Hidradenitis suppurativa, also known as acne inversa, is a pyoderma gangrenosum. Initially seen in 1971, a 20-year chronic and recurrent inflammatory skin disease that follow-up of this patient was presented in 1992 [4] and we initially presents as tender subcutaneous nodules which now provide a 40-year follow-up (Case 1). coalesce into deep dermal abscesses [22]. The lesions occur Rosner et al. described a similar spondyloarthropathy most frequently in apocrine-gland bearing areas of the skin association with hidradenitis suppurativa and acne such as axillae, inguinal, perianal and perineal, mammary conglobata [5]. Ten adult patients were seen, and all but and inframammary, and buttock regions [22, 23]. Long one were African-Americans. Similar case reports showed thought to be a result of within the apocrine the same trend [6–10, 14]. Dissecting cellulitis of the scalp, gland itself, many now believe the inciting factor is a rare suppurativa disease characterized by painful scalp follicular plugging with resultant occlusion and rupture nodules and alopecia, has also been described either alone [24]. The subsequent influx of inflammatory cells leads to or in combination with acne or hidradenitis, with formation and fistulous tracts. The disease typically spondyloarthropathy [12, 29]. occurs after puberty, with a peak incidence in the second or third decades, and is significantly more common in females [22]. Some authors have suggested a higher prevalence Illustrative Cases among African-Americans, but this has not been substan- tiated by studies examining racial predilection [24]. Case 1 This case had previously been reported in 1981 and 1992, and we now provide another follow-up. He is an African-American, now 66 years old, who has had Dissecting Cellulitis of the Scalp hidradenitis suppurativa since age 16, affecting the groin and axillary regions. He initially saw one of us (M.A.K.) in Dissecting cellulitis of the scalp, also called perifolliculitis 1971 when he had presented with pain in the left wrist and capitis abscendens et suffodiens, is a rare, chronic, relapsing, hand, and episodes of pain and inflammation of the knees, suppurativa disease characterized by painful fluctuant scalp ankles and feet. He had a past history of an episode of nodules and abscesses that heal with patchy areas of scarring painful pustular lesions on his left leg that were diagnosed and alopecia [16•]. The lesions usually begin on the occiput or by skin biopsy as pyoderma gangrenosum. Gastrointestinal vertex as a and then expand into patches of evaluation including barium enema and sigmoidoscopy perifollicular pustules, nodules, abscesses and sinuses [25]. were negative. He responded to treatment with short courses This condition predominantly occurs in African-American of , erythromycin and surgical excision of his men aged 20–40 years of age but has been described rarely in hidradenitis lesions. other ethnic groups as well as among females [25–27]. The In June 1981, he developed increasing groin drainage etiology is unknown, but follicular occlusion, immune- accompanied by dactylitis of his right third finger and mediated chronic inflammation, and infection have all been an inflammatory arthritis involving his right third implicated in the pathogenesis [28]. metacarpophalangeal (MCP) and proximal interphalangeal Dissecting cellulitis of the scalp may occur alone, but (PIP) joints. Aspiration from the right third MCP joint revealed when seen in combination with acne conglobata and a white count of 16,000 with 89 % polymorphonuclear cells hidradenitis suppurativa, is referred to as the follicular with negative gram stain and culture. One month later, he occlusion triad [16•, 29]. developed right groin and trochanteric pain with marked difficulty walking for which he was hospitalized. Physical examination demonstrated worsening of his acne and Historical Aspect increased drainage of his groin abscesses. Joint pain and tenderness of the third MCP and PIP joint of the right hand In 1959, Burns and Coleville [1] reported a case of a 16- persisted, and he was noted to have pain with external rotation year-old Caucasian male with fever, severe acne conglobata of the hip. Erythrocyte sedimentation rate was 28. He lacked and arthralgia, with no objective joint findings. On follow- rheumatoid factor and HLA-B27, and his ANA was initially up, he later did develop erosive arthritis of the right knee negative. Bone scan showed increased uptake in the [2]. There was also a report in 1961 of a 15-year-old symptomatic finger joints with mildly increased uptake over Curr Rheumatol Rep (2013) 15:346 Page 3 of 8, 346 the right hip joint. Hand films showed early erosive change in 2 weeks of rifampin and clindamycin in Dermatology clinic right MCP joint. Gram stain and culture of fluid obtained from for acne as well as dissecting cellulitis of the scalp and right hip aspiration was negative. He was then started on sycoses barbae of the chin area. He was currently using prednisone 18 mg/day with prompt improvement in his joint transretinoin cream to the face and fluocinonide 0.05 % symptoms as well as his skin lesions. His prednisone dose was cream on the scalp. gradually tapered off over the next several months, as his joint On examination, he was noted to have eroded superficial symptoms and skin lesions completely resolved. scars with deep pits over the right cheek. Over the vertex of He did not subsequently come for follow-up until the scalp were a few abscesses and multiple, crusted tender September 2007, when he presented with pain in his left nodules with patchy alopecia. He showed clinical features wrist and dorsum of the hand for 2 weeks. He stated that he of ankylosing spondylitis. Axial rotations and lateral flexion had not had any severe flares of joint pain over the past of his neck were markedly restricted. Schober test showed 20 years until this episode. He denied any history of urinary limited lumbar spinal mobility (10 → 12 cm) He was also or gastrointestinal symptoms, and had no history of physical noted to have left Achilles tendonitis and warmth of the left injury. He stated that his hidradenitis had also been well knee with pain on terminal extension. controlled, but had recently developed one lesion involving Laboratory studies were notable for thrombocytosis with his left earlobe. This time, his ANA was positive at 1:320. platelet count of 633 and hemoglobin of 11.5 mg/dL with He was anti-dsDNA negative and with no clinical evidence normal MCV. His ESR and CRP were 107 mm/h and of lupus or other related auto-immune diseases. On 4.3 mg/dL, respectively. Pelvis x-ray revealed bilateral examination, the lesion on his earlobe was swollen and sacroiliitis with erosions and juxta-articular bony sclerosis. draining but he had no other active skin lesions. His left Lumbar spine x-ray revealed syndesmophyte formation wrist and dorsum of the hand were swollen and tender, with along the lumbar vertebrae. The intervertebral disc spaces pain on both active and passive range of motion. The wrist and vertebral body heights were intact. Imaging of the joint did not yield any fluid on aspiration and he responded cervical spine, including magnetic resonance imaging to intra-articular hexoacetonide (Aristospan). (MRI) revealed bridging syndesmophytes from 3rd to 6th The hidradenitis lesion of his left earlobe responded to cervical vertebrae, with also some calcification of the intralesional injection of triamcinolone acetonide anterior longitudinal ligament. HLA B27 test was negative. (Kenalog). Upon return to the clinic 2 weeks later, the His Bath Ankylosing Spondylitis Disease Activity Index wrist pain had improved but he had developed medial (BASDAI) was calculated to be 5.2 (on a scale of 0 to 10; epicondylitis of his left elbow and tenosynovitis of the 10 being worse) despite conventional treatment with flexor tendon of left thumb. These responded very well to a NSAIDs. After obtaining a negative PPD and hepatitis short course of 20 mg of daily oral prednisone therapy serologies, he was begun on adalimumab 40 mg subcuta- which was then tapered. His residual hidradenitis lesion of neously every other week for his spondylitis and Achilles his left earlobe also responded well to repeat intralesional tendonitis. There was marked symptomatic improvement, triamcinolone injections. He has not come back for follow- resolution of Achilles tendonitis and knee synovitis, and his up for his skin and joint symptoms. BASDAI score decreased to 1.2. He did not come for follow-up for nearly 2 years because he had moved to Case 2 This is a 29-year-old African-American male who California, but has remained on adalimumab every 2 weeks was referred to our clinic in 2002 for the evaluation of a with continued excellent response. He recently returned positive anti-nuclear antibody (ANA) test. There was no back to Ohio and on follow-up in our clinic was found to be clinical evidence of SLE. He stated that he had been seen at asymptomatic and free of any skin lesions. several emergency rooms for symptoms of inflammatory low back and neck pain with morning stiffness. He had been Case 3 A 36-year = old African-American male was seen in prescribed various muscle relaxants and non-steroidal anti- November 2007 for a 3-month history of right hand and inflammatory drugs (NSAIDs) with minimal relief. His wrist pain with associated swelling. He had also noted subsequent course had also been complicated by intermit- intermittent pain in the third and fourth digit of his left hand tent episodes of knee pain as well as heel pain which made as well as the right elbow, with only minimal relief with it difficult to ambulate. He denied episodes of eye pain or various NSAIDs. He denied any fever, weight loss, episodes redness, oral ulcers, genital discharge or urinary symptoms. of eye pain or redness, gastrointestinal or urinary symptoms, He had noted a 40–pound (c. 18-kg) weight loss over the or back pain, but mentioned that he has had a large keloidal preceding 6 months. His family history was negative for plaque at the base of his scalp which had been treated with inflammatory bowel disease (IBD), skin disease or triamcinolone acetonide injections by Dermatology in the spondylitis. He gave a long history of acne vulgaris, which past. There was no family history of psoriasis or IBD. On began as a teenager, and more recently was treated with examination, there was a large keloidal plaque with crusted 346, Page 4 of 8 Curr Rheumatol Rep (2013) 15:346 areas over his posterior scalp. There was mild limitation of his scalp and cheeks. He was diagnosed with acne, full extension at the right elbow. The right wrist had mildly hidradenitis and dissecting cellulitis of the scalp. Treatment increased warmth as well as tenderness and pain with range of his skin included multiple courses of antibiotics, of motion. There was diffuse swelling of the digits with dapsone, blue light and laser therapy. tenderness over several MCP and PIP joints of the right On physical examination, he was noted to have scattered hand. There were no sausage digits. Laboratory studies erythematous papules, nodules, and pustules on his showed an ESR of 42 mm/h and a CRP of 8.6 mg/dL. chin and over his occipital scalp and anterior chest area. Rheumatoid factor and anti-CCP tests were negative. A There was no swelling or tenderness of his peripheral joints right hand x-ray showed a small erosion at the base of the and he had no limitation of spinal range of motion. No second proximal phalanx and a larger erosion of the sacroiliac joint tenderness was elicited. triquetral carpal bone. MRI of the right wrist showed Laboratory work revealed a low positive ANA 1:40, with extensive synovitis within the wrist with associated erosive a fine speckled pattern. His ENA panel was negative as was changes and marrow edema. Thickening of the tendon his rheumatoid factor. His CRP was 1.3 mg/dL. HLA-B27 sheaths was also noted. was negative. Although ordered, the patient did not go to He was then started on methotrexate 15 mg/week and Radiology for imaging of his SI joints. prednisone 10 mg/day with which he noted marked The patient was diagnosed with a form of reactive improvement in his joint symptoms. He was weaned off arthritis associated with his dissecting cellulitis, acne and prednisone, and methotrexate was increased to 20 mg/week. hidradenitis. He responded very well to prednisone 20 mg He did well until September 2008 when he noted increased with resolution of his symptoms. The patient was later put left hand pain and swelling. Concurrently with this arthritic on sulfasalazine and the prednisone was tapered off. flare, he noticed a draining lesion under the left armpit. Examination showed mild synovitis of the left wrist and left Case 5 A 56-year-old African-American male was referred 2nd and 3rd MCP joint. His axillae showed draining sinus to the arthritis clinic for evaluation of bilateral hand pain. tracts which Dermatology confirmed were consistent with His symptoms started 3 years before with intermittent hidradenitis, a new diagnosis for this patient. He subse- swelling of his fingers, and resulted in deformities quently also developed left ankle and mid foot involvement particularly affecting his right hand. He was diagnosed as well as dactylitis of the right 3rd and 4th toes. These with hidradenitis suppurativa at the age of 13 years. He symptoms responded dramatically to prednisone 10 mg/day. described the pain in his hands as dull and aching, and it Leflunomide 10 mg/day was also added to his regimen. His was exacerbated during flare-ups of his hidradenitis. The prednisone was subsequently weaned off and his joint joint pains were only partially responsive to ibuprofen symptoms have been stable. The hidradenitis lesions are which he took 3 times a day. He denied fever, weight loss, being treated with dapsone by Dermatology. Interestingly, a back pain, episodes of eye pain or redness, gastrointestinal repeat right hand x-ray showed marked improvement in the or urinary symptoms. prominent demineralization which had been seen 1 year On exam, the patient was noted to have cystic acne prior to starting DMARDs. involving the face and hidradenitis suppurativa lesions of his left axillae and bilateral groin areas. Examination of his Case 4 A 29-year-old African American male, with a 9- joints revealed non-tender Boutonnière deformities of his year history of acne keloidalis, hidradenitis suppurativa and right 2nd, 3rd and 4th fingers, with some warmth and dissecting cellulitis of the scalp was referred to the arthritis tenderness of his right 5th DIP joint. Grip strength was clinic for evaluation of joint pains. The patient described a reduced in his right hand. He had bilateral ankle warmth, 4-month history of unbearable “soreness” in his neck, tenderness and swelling. Examination of his spine and shoulders and upper chest region. He complained of sacroiliac joints was normal. episodes of migratory joint pain and swelling that would Laboratory testing was notable for negative rheumatoid involve his knees, ankles, feet or fingers at various times factor and negative antibodies to CCP. Imaging of his hands and that would usually resolve spontaneously within 3 days. revealed an asymmetric erosive arthropathy mainly affect- At the time of his visit, he complained of lower back pain of ing the right 3rd MCP, carpal bones and ulnar styloid. 2 weeks duration. The patient described stiffness in his The patient was diagnosed with a reactive arthritis lower back that would be worse after periods of inactivity associated with his acne and hidradenitis suppurativa. He and would improve after stretching and walking. He did not was started on prednisone 20 mg daily with good response. have any gastrointestinal symptoms and denied episodes of He was seen by Dermatology for treatment of his eye pain or redness. hidradenitis suppurativa, and was started on doxycycline, The patient had been followed in the Dermatology clinic with subsequent improvement in his . The since 2001 when he developed acne-like lesions affecting patient received intra-articular steroid injections to the right Curr Rheumatol Rep (2013) 15:346 Page 5 of 8, 346 wrist and right 2nd and 3rd PIPs due to persistent synovitis, upper extremity joints in all cases. In two of the cases, the with good response. At subsequent visits, his prednisone lower extremity joints were also affected. Three of the cases dose was tapered off. with available imaging revealed erosive changes on x-ray. Case 2 presented with axial symptoms due to spondylitis (with bilateral sacroiliitis and syndesmophytes), accompa- Discussion nied by knee synovitis and Achilles tendinitis. This patient was HLA-B27 negative. Case 4 had inflammatory back Table 1 summarizes the main characteristics of our cases. pain but did not have imaging to review. Interestingly, all our patients were African-American males. Bhalla and Sequeira reviewed 29 cases of arthritis Although other races can be affected, prior published case associated with hidradenitis and acne conglobata and series show predominance of African Americans [5, 13]. summarized their findings [13]. Of these patients, 11 had This predilection may partly be explained by the fact that hidradenitis alone, 5 had acne conglobata, 7 had both hidradenitis suppurativa has a higher incidence in African- entities, and 6 fulfilled criteria for the follicular occlusion Americans [30]. This may also simply reflect the population triad. The average age was 35 years with a male:female served at our medical center in Cleveland, as is probably the ratio of 20:9. African-Americans were the predominant case for the study done by Bhalla et al. in Chicago [13]. ethnic group although five Caucasians and one Asian were In all our cases, the skin condition was present before the also reported. There were no reports of constitutional onset of arthritis. The timing of the first onset of arthritis symptoms such as fever or weight loss. Clinical character- from the appearance of skin disease ranged from 2 to istics include both an asymmetric peripheral arthritis and 40 years. Three of our patients clearly demonstrated a axial disease. Patients were noted to have an inflammatory temporal relationship between arthritis flares and flares in oligoarthritis involving both upper and lower extremities. their skin disease, a finding in keeping with prior published The knees were most commonly affected in this series, but cases [13]. Four of the five patients we presented had the wrists, ankles, elbows and small joints of the hands and features of a peripheral asymmetrical arthritis affecting the feet were also frequently involved.

Table 1 Summary of clinical and radiographic characteristics of five illustrative cases

Case 1 Case 2 Case 3 Case 4 Case 5

Age/Sex/Race 66 M AA 29 M AA 36 M AA 29 M AA 56 M AA Skin condition HS DCS HS HS HS PG Acne vulgaris Keloid plaque DCS Cystic acne Sycoses barbae Acne keloidalis Onset of skin disease 16 Teenage years (13–18) 31 20 13 (age in years) Onset of arthritis in 10 years after 5–10 years after (onset age 23) 2 years after 3 years after 40 years after relation to Skin Lesions Type of arthritis Peripheral (UE/LE) Ankylosing spondylitis Peripheral (UE) Peripheral (UE/LE) Peripheral (UE) Peripheral (LE) Axial Achilles tendonitis Migratory LE HLAB27/RF/ANA (−)/(−)/a (−)/NT/(+) NT/(−)/NT (−)/(−)/(+) NT/(−)/NT Imaging findings Erosive (hand) Syndesmophytes Erosive (hand) Unavailable Erosive(hand) Sacroiliitis Treatment Oral CS NSAIDS Oral CS Oral CS Oral CS IA CS Adalimumab Methotrexate Sulfasalazine IA CS Leflunomide Temporal relationship Yes Yes Yes between skin and joint disease

NT Not tested, CS , PG pyoderma gangrenosum, IA intra-articular, DCS Dissecting cellulitis of scalp, HS hidradenitis suppurative, UE/LE upper extremity/lower extremity a Initially negative, but became positive at 1:320 after several years. Anti-dsDNA negative and with no clinical evidence of lupus or other related auto-immune diseases 346, Page 6 of 8 Curr Rheumatol Rep (2013) 15:346

The arthritis associated with hidradenitis suppurativa is Laboratory evaluation reveals a mild anemia, normal or generally more asymmetric and peripheral on initial moderately elevated white blood cell count and platelet presentation, while axial involvement, which tends to be count. Erythrocyte sedimentation rate is commonly elevated less severe and often asymptomatic, occurs later. In contrast, in these patients. Complement (C3 and C4) levels were 72 % of acne conglobata patients have sacroiliitis that is elevated in a third of patients in Bhalla’s series [13]. There more commonly symptomatic [13]. In 1993, Rosner et al. is no association with rheumatoid factor [12, 13]. In one described 21 patients with hidradenitis and/or acne series, 6 out of 20 patients had a positive ANA test, with conglobata and an associated inflammatory arthropathy. titers ranging from 1:20 to 1:640 [12]. ANA titers of 1:80 Eighteen patients had a peripheral arthritis, 15 presented were found in 2 out of 9 patients in another series, which with axial disease and 12 patients exhibited symptoms of were negative when repeated [13]. One of our patients had a both [12]. Sacroiliitis is often unilateral .The cervical spine negative ANA test which later became positive at 1:320, may also be involved though usually to a lesser degree than with a negative anti-dsDNA and with no clinical evidence lumbosacral involvement. Three patients also had calcifi- of lupus or other related auto-immune diseases. The cation of the anterior longitudinal ligament [13]. majority of cases are HLA-B27 negative. The three patients The onset of arthritis usually followed the skin condition that have been reported to possess HLA-B27 had grade 3 or by 1–20 years, but there have been case reports of arthritis 4 sacroiliitis [12, 17••]. preceding skin disease [6, 31]. Bhalla et al. noted The most common radiographic features in patients with exacerbation of joint symptoms coinciding with flares of arthritis-associated hidradenitis suppurativa and acne skin disease in a majority of patients, a finding that has been conglobata were peripheral joints erosions followed by noted in other series as well as in our patients [13]. periarticular osteoporosis, periosteal reaction and new bone Similarly, with dissecting cellulitis of the scalp, the arthritis formation [13]. Bony erosions were often noted bilaterally tends to follow the remitting and relapsing activity of the in symmetrical joints [12]. Others have noted similar skin disease [15]. radiographic findings as well as periarticular osteopenia There was a 40-year time lag between onset of skin [12]. Our first case was found to have erosion of the MCP lesions and arthritis for one of our patients, with the joint joint of the finger affected with dactylitis; a similar symptoms coinciding with flare-ups of his hidradenitis occurrence has recently been reported [16•]. Axial skeletal suppurativa. Another patient reported by Laber et al. had involvement (with unilateral or bilateral sacroiliitis and arthritis that started concurrently with development of acne spinal involvement with squaring of the vertebrae and conglobata but remained active 12 years after resolution of syndesmophyte formation, often distributed asymmetrical- skin symptoms [18]. Persistence of these symptoms, and the ly) has been reported [12]. occasional case reports of prolonged time lags between occurrence of skin disease and arthritis, led the authors to hypothesize that the associated arthritis is a chronic and Treatment progressive inflammatory disorder that becomes more apparent Although NSAIDs can be beneficial, the response to The pathogenesis of this arthritis is unknown. The initial NSAIDs in our patient group seemed to be suboptimal. description of acne-associated arthralgia by Burns sug- Four out of five of our patients were started on oral gested the presence of septicemia [1], and many patients corticosteroids. Two out of four patients were controlled with acne fulminans have presented with septic pictures with just oral corticosteroids and intra-articular injection of requiring extensive work-up. With very few exceptions a few joints when needed. Non-biologic DMARDs were though, bacterial cultures have been negative and the added in two cases, with sulfasalazine in case 4 and presence of infection as a possible pathophysiological methotrexate in case 3. Case 2 who had mainly axial mechanism have not been substantiated. symptoms was treated with adalimumab with excellent and Windom speculated that the arthritis in acne conglobata rapid response that has been sustained to date. represented an association similar to that observed with Treatment strategies recommended by Hazen et al. for ulcerative colitis [3]. A possible mechanism postulated by hidradenitis suppurativa included antibiotics, intralesional some authors involves a hypersensitivity response to sebum, or systemic steroids, electrosurgery, colchicine, dapsone, altered skin antigens, or bacterial antigens involved in acne and biologics for early and middle stage disease, with [13, 32]. However, the fact that patients can present with excision or incision and drainage of affected areas for more arthritis before skin disease challenges this hypothesis [6, 31]. advanced disease [33•]. Some patients reported improve- Reports of positive circulating immune complexes/ANAs [12] ment of arthritis after surgical therapy of scalp cellulitis and and response of some of the patients to prednisone and/or hidradenitis suppurativa [5]. Carbon dioxide laser excision DMARDs may also indicate an autoimmune phenomenon. and marsupialization offer a novel approach to the Curr Rheumatol Rep (2013) 15:346 Page 7 of 8, 346 management of persistent or late stage hidradenitis factor and HLA-B27 testing is usually negative in this suppurativa lesions [33•], although the effect of this group of patients. Imaging of peripheral joints may reveal treatment on arthritis is unknown. erosions, periosteal bone reaction, and new bone formation. Various treatment modalities have been used in the When the axial skeleton is involved, imaging can reveal management of arthritis associated with hidradenitis sacroiliitis, syndesmophyte formation, squaring of the suppurativa, dissecting cellulitis of the scalp and acne. vertebrae, and, rarely, calcification of the anterior longitu- Nonsteroidal anti-inflammatory agents and prednisone [13– dinal ligament. NSAIDs, oral and intra-articular steroids, 15] have been used with some success as well as disease and DMARDs have all been used with success. As modifying anti-rheumatic drugs (DMARDs) such as illustrated by one of our patients with ankylosing sulfasalazine [29] and methotrexate [13]. Libow et al. spondylitis and Achilles tendonitis resistant to conventional reported a marked improvement in arthritis in a patient with therapy, TNF alpha antagonists are dramatically effective. acne, hidradenitis and dissecting cellulitis of the scalp using However, controlled trials with larger numbers of patients oral [34], though cases of sacroiliitis induced by are needed to assess which treatment options are the most isotretinoin have also been described [35]. Some case series effective for this group of patients. have also reported a favorable response to surgical excision of the hidradenitis lesions [13]. Compliance with Ethics Guidelines The off-label use of TNF antagonists is being increas- Conflict of Interest Debbie T. Lim declares that she has no conflicts ingly reported to be effective in treating both the of interest. dermatologic and musculoskeletal manifestations of these Neena M. James declares that she has no conflicts of interest. diseases. Infliximab was first used for hidradenitis Sobia Hassan declares that she has no conflicts of interest. suppurativa in the setting of Crohn’s disease, with Muhammad Asim Khan declares that he has no conflicts of interest. improvement in both joint and cutaneous symptoms noted Human and Animal Rights and Informed Consent This article [36, 37]. Since then, cases of hidradenitis and acne does not contain any studies with human or animal subjects performed conglobata as well as dissecting cellulitis of the scalp have by any of the authors. been treated with infliximab, adalimumab and etanercept with success [17••, 19, 38•, 39•, 40–42]. Interestingly, however, cases of new-onset polyarthritis during successful References treatment of hidradenitis suppurativa with Infliximab were recently described, with the underlying mechanism for this Papers of particular interest, published recently, have been still unknown [39•]. Infliximab and adalimumab [17••, 43] highlighted as: have both been shown to be effective in patients with • Of importance reactive arthritis or spondyloarthropathy in association with •• Of major importance hidradenitis and acne conglobata. Our case 2 illustrates dramatic and sustained efficacy of adalimumab to treat 1. Burns RE, Coleville JM. Acne conglobate with septicemia (?). dissecting cellulitis of the scalp and associated spondylitis Arch Dermatol. 1959;104:151–3. and Achilles tendonitis resistant to conventional 2. Kelly AP, Burns RE. Acute febrile ulcerative conglobate. Arch management. Dermatol. 1971;104:182–7. 3. Windom RE, Sanford JP, Ziff M. Acne conglobata and arthritis. Arthritis Rheum. 1961;4:632–5. 4. Olafsson S, Khan MA. Musculoskeletal features of acne, Conclusions hidradenitis suppurativa, and dissecting cellulitis of the scalp. Rheum Dis Clin N Am. 1992;18(1):215–24. In conclusion, the association of sero-negative arthritis with 5. Rosner IA, Richter DE, Huettner TL, Kuffner GH, Wisnieski JJ, Burg CG. Spondyloarthropathy associated with hidradenitis suppurativa acne conglobata, hidradenitis suppurativa, and dissecting and acne conglobata. Ann Intern Med. 1982;97:520–5. cellulitis of the scalp is now well established, but it is 6. Bennett RE, Wilke WS, Murphy DP. Spondyloarthropathy and relatively uncommon and can be overlooked. To re- hidradenitis suppurativa. Ann Intern Med. 1983;97(1):112 (Letter emphasize this association and to add to the current to the editor). 7. Vasey FB, Fenske NA, Clement GB, Bridgeford PH, Germain BF, literature, we present these five illustrative cases. Both Espinoza LR. Immunological studies of the arthritis of acne asymmetric peripheral arthritis and spondylitis can occur. conglobata and hidradenitis suppurativa. Clin Exp Rheumatol. Although not exclusive to African-Americans, there may be 1984;2(4):309–11. a predominance of arthritis in this group. The arthritis is 8. Kenik J, Hurley J. Arthritis occurring with hidradenitis suppurativa. J Rheumatol. 1985;12(1):183–4 (Letter to the editor). usually insidious and occurs after the onset of the skin 9. Ellis BI, Shier CK, Leisen JJC, Kastan DJ, McGoey JW. Acne- disease. In addition, a temporal relationship between flares associated spondyloarthropathy: radiographic features. Radiology. in skin and joint disease is well described. Rheumatoid 1987;162:541–5. 346, Page 8 of 8 Curr Rheumatol Rep (2013) 15:346

10. Grassi W, Offidani AM, Blasetti P, Simonetti O, Cervini C. HLA- 27. Ramesh V. Dissecting cellulitis of the scalp in 2 girls. B27 negative ankylosing spondylitis and hidradenitis suppurativa: Dermatologica. 1990;180(1):48–50. report of a case. Clin Rheumatol. 1988;7(2):278–84. 28. Dyall-Smith D. Signs, syndromes and diagnoses in dermatology: 11. Hellman D. Spondyloarthropathy with hidradenitis suppurativa. dissecting cellulitis of the scalp. Austral J Dermatol. 1993;34:81–2. JAMA. 1992;267(17):2363–5. 29. Thein M, Hogarth MB, Acland K. Seronegative arthritis 12. Rosner IA, Burg CG, Wisnieski JJ, Schacter BZ, Richter DE. The associated with the follicular occlusion triad. Clin Exp Dermatol. clinical spectrum of the arthropathy associated with hidradenitis 2004;29(5):550–2. suppurativa and acne conglobata. J Rheumatol. 1993;20:684–7. 30. Kelly P. Dermatology. In: Bolognia JL, Jorizzo JL, editors. 13. Bhalla R, Sequeira W. Arthritis associated with hidradenitis Folliculitis and the follicular occlusion tetrad, vol. 1. London: suppurativa. Ann Rheum Dis. 1994;53(1):64–6. Mosby; 2003. p. 564–6. 14. Leybishkis B, Fasseas P, Ryan KF, Roy R. Hidradenitis suppurativa 31. Tallo R, Quinet R, Waxman J. Reactive arthritis due to and acne conglobata associated with spondyloarthropathy. Am J Med hidradenitis suppurativa mimicking osteomyelitis. South Med Sci. 2001;321(3):195–7. J. 1991;84(9):1147–9. 15. Salim A, David J, Holder J. Dissecting cellulitis of the scalp with 32. Knitzer RH, Needleman BW. Musculoskeletal syndromes associ- associated spondyloarthropathy: case report and review. J Eur ated with acne. Semin Arthritis Rheum. 1991;20(4):247–55. Acad Dermatol Venereol. 2003;17:689–91. 33. • Hazen PG, Hazen BP. Hidradenitis suppurativa: successful 16. • Fioravanti A, Flori ML, Guidelli GM, Giordano N. Dactylitis as treatment using carbon dioxide laser excision and marsupialization. a first manifestation of arthritis associated with hidradenitis Dermatol Surg. 2010;36:208–12. Treatment strategies for suppurativa. Indian J Dermatol Venereol Leprol. 2011;77:74–6. hidradenitis suppurativa, offering a novel approach to management (Letter to the editor). The patient presented here had dactylitis and of late stage lesions. erosion of the MCP joint, similar to that of our first case. 34. Libow LF, Friar DA. Arthropathy associated with cystic acne, 17. •• Bruzzese V.Pyoderma gangrenosum, acne conglobata, suppurativa hidradenitis suppurativa, and perifolliculitis capitis abscedens et hidradenitis, and axial spondyloarthritis: efficacy of anti-tumor suffodiens: treatment with isotretinoin. Cutis. 1999;64(2):87–90. necrosis factor * therapy. J Clin Rheum. 2012;18(8):413–5. This 35. Bachmeyer C, Charoud A, Turc Y, Callot V, Blum L, patient had HLA-B27+ bilateral sacroiliitis. Most of the patients Aractingi S. Isotretinoin-induced bilateral sacroiliitis. Derma- reported in previous literature were HLA-B27 negative. This case is tology. 2003;206(3):285–6. the 3rd so far that was HLA-B27 positive. Regression of both 36. Katsanos KH, Christodoulou DK, Tsianos EV. Axillary hidradenitis cutaneous and spondyloarthritic symptoms were noted with anti-TNF suppurativa successfully treated with infliximab in a Crohn’sdisease therapy, just as in case of one of our patients (case 2). patient. Am J Gastroenterol. 2002;97:2155–6 (Letter to the editor). 18. Laber DA, Ravakhah K, Smite HR. Acne conglobata associated 37. Roussomoustakaki M, Dimoulios P, Chatzicostas C, Kritikos HD, with spondyloarthropathy and ankylosis of the wrists. J Clin Romanos J, Panayiotides JG, et al. Hidradenitis suppurativa Rheumatol. 1999;5:162–72. associated with Crohn’s disease and spondyloarthropathy: re- 19. Shirakawa M, Uramoto K, Harada FA. Treatment of acne conglobata sponse to anti-TNF therapy. J Gastroenterol. 2003;38:1000–4. with infliximab. J Am Acad Dermatol. 2006;55(2):344–6. 38. • Mansouri Y, Martin-Clavijo A. Dissecting cellulitis of the scalp 20. Zaenglein AL, Graber EM, Thiboutot DM, Strauss JS. Chapter 78. successfully treated with infliximab. J Am Acad Dermatol. Acne vulgaris and acneiform eruptions. In: Wolff K, Goldsmith 2012;66(4):AB98. A successful treatment of dissecting cellulitis LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. of the scalp with infliximab. Fitzpatrick’s dermatology in general medicine. 7th ed. New York: 39. • Van Rappard DC, Mooij JE, Baeten DLP, Mekkes JR. New-onset McGraw-Hill; 2008. polyarthritis during successful treatment of hidradenitis suppurativa 21. Jansen T, Plewig G. Acne fulminans. Int J Dermatol. with infliximab. Br J Dermatol. 2011;165(1):194–8. A report of an 1998;37:254–7. unexpected new-onset polyarthritis after infliximab treatment. 22. Slade DEM, Powell BW, Mortimer PS. Hidradenitis suppurativa: 40. Moul DK, Korman NJ. Severe hidradenitis suppurativa treated pathogenesis and management. Br J Plast Surg. 2003;56:451–61. with adalimumab. Arch Dermatol. 2006;142:1110–2. 23. Habif TP. Clinical dermatology: a color guide to diagnosis and 41. Sukhatme SV, Lenzy YM, Gottlieb AB. Refractory dissecting therapy. NY: Mosby; 2004. cellulitis of the scalp treated with adalimumab. Drugs Dermatol. 24. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a 2008;7(10):981–3. comprehensive review. J Am Acad Dermatol. 2009;60:539–61. 42. Cusack C, Buckley C. Etanercept: effective in the management of 25. Scheinfeld NS. A case of dissecting cellulitis and a review of the hidradenitis suppurativa. Br J Dermatol. 2006;154:726–9. literature. Dermatol Online J. 2003;9(1):8. 43. Scheinfeld N. Treatment of coincident seronegative arthritis and 26. Stites PC, Boyd AS. Dissecting cellulitis in a white male: a case hidradenitis suppurativa with adalimumab. J Am Acad Dermatol. report and review of the literature. Cutis. 2001;67(1):37–40. 2006;55(1):163–4 (Letter to the editor).